Schizophrenia Research
Volume 120, Issue 1 , Pages 131-142 , July 2010

Convergent Evidence Shows a Positive Association of Interleukin-1 Gene Complex Locus with Susceptibility to Schizophrenia in the Caucasian population

  • Mingqing Xu

      Affiliations

    • School of Public Health, Harvard University, Boston, MA 02115, USA
    • Department of Medicine, Brigham and Women's Hospital, Medical School, Harvard University, Boston, MA 02115, USA
    • Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Center, Shanghai Jiao Tong University, Shanghai 200030, PR China
    • Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China
    • Corresponding Author InformationCorresponding authors. Mingqing is to be contacted at Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. Lin He is to be contacted at Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China or Institute for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, PR China.
    • ,
  • Lin He

      Affiliations

    • Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Center, Shanghai Jiao Tong University, Shanghai 200030, PR China
    • Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China
    • Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China
    • Corresponding Author InformationCorresponding authors. Mingqing is to be contacted at Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. Lin He is to be contacted at Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China or Institute for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, PR China.

Received 5 June 2009 ,Revised 7 February 2010 ,Accepted 9 February 2010.

References 

  1. Akiyama K. Serum levels of soluble IL-2 receptor α, IL-6 and IL-1 receptor antagonist in schizophrenia before and during neuroleptic administration. Schizophr. Res. 1999;37:97–106
  2. Allen NC, Bagade S, McQueen MB, Ioannidis JP, Kavvoura FK, Khoury MJ, et al. Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat. Genet. 2008;40:827–834
  3. Baker I, Masserano J, Wyatt RJ. Serum cytokine concentrations in patients with schizophrenia. Schizophr. Res. 1996;20:199–203
  4. Barak V, Barak Y, Levine J, Nisman B, Roisman I. Changes in interleukin-1β and soluble interleukin-2 receptor levels in CSF and serum of schizophrenic patients. J. Basic Clin. Physiol. Pharmacol. 1995;6:61–69
  5. Bessler H, Levental Z, Karp L, Modai I, Djaldetti M, Weizman A. Cytokine production in drug-free and neuroleptic-treated schizophrenic patients. Biol. Psychiatry. 1995;38:297–302
  6. Betcheva ET, Mushiroda T, Takahashi A, Kubo M, Karachanak SK, Zaharieva IT, et al. Case-control association study of 59 candidate genes reveals the DRD2 SNP rs6277 (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian population. J. Hum. Genet. 2009;54:98–107
  7. Chowdari KV, Xu K, Zhang F, Ma C, Li T, Xie BY, et al. Immune related genetic polymorphisms and schizophrenia among the Chinese. Hum. Immunol. 2001;62:714–724
  8. Danis VA, Millington M, Hyland VJ, Grennan D. Cytokine production by normal human monocytes: inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism. Clin. Exp. Immunol. 1995;99:303–310
  9. Hänninen K, Katila H, Saarela M, Rontu R, Mattila KM, Fan M, et al. Interleukin-1 beta gene polymorphism and its interactions with neuregulin-1 gene polymorphism are associated with schizophrenia. Eur. Arch. Psychiatry Clin. Neurosci. 2008;258:10–15
  10. Hulkkonen J, Laippala P, Hurme M. A rare allele combination of the interleukin-1 gene complex is associated with high interleukin-1β plasma levels in healthy individuals. Eur. Cytokine Netw. 2000;11:251–255
  11. Hurme M, Santtila S. IL-1 receptor antagonist (IL-1Ra) plasma levels are co-ordinately regulated by both IL-1Ra and IL-1β genes. Eur. J. Immunol. 1998;28:2598–2602
  12. Katila H, Hänninen K, Hurme M. Polymorphisms of the interleukin-1 gene complex in schizophrenia. Mol. Psychiatry. 1999;4:179–181
  13. Kilpinen S, Huhtala H, Hurme M. The combination of the interleukin-1alpha (IL-1alpha-889) genotype and the interleukin-10 (IL-10 ATA) haplotype is associated with increased interleukin-10 (IL-10) plasma levels in healthy individuals. Eur. Cytokine Netw. 2002;13:66–71
  14. Kim YK, Lee MS, Suh KY. Decreased interleukin-2 protein in Korean schizophrenic patients. Biol. Psychiatry. 1998;43:701–704
  15. Kim SJ, Lee HJ, Koo HG, Kim JW, Song JY, Kim MK, et al. Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder. Psychiatr. Genet. 2004;14:165–167
  16. Laurent C, Thibaut F, Ravassard P, Campion D, Samolyk D, Lafargue C, et al. Detection of two new polymorphic sites in the human interleukin-1 beta gene: lack of association with schizophrenia in a French population. Psychiatr. Genet. 1997;7:103–105
  17. Li D, Collier DA, He L. Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia. Hum. Mol. Genet. 2006;15:1995–2002
  18. Licinio J, Seibyl JP, Altemus M, Charney DS, Krystal JH. Elevated CSF levels of interleukin-2 in neuroleptic-free schizophrenic patients. Am. J. Psychiatry. 1993;150:1408–1410
  19. Maes M, Bosmans E, Ranjan R, Vandoolaeghe E, Meltzer HY, De Ley M, et al. Lower plasma CC16, a natural anti-inflammatory protein, and increased plasma interleukin-1 receptor antagonist in schizophrenia: effects of antipsychotic drugs. Schizophr. Res. 1996;21:39–50
  20. Maury CP, Liljeström M, Laiho K, Tiitinen S, Kaarela K, Hurme M. Anaemia of chronic disease in AA amyloidosis is associated with allele 2 of the interleukin-1beta-511 promoter gene and raised levels of interleukin-1beta and interleukin-18. J. Intern. Med. 2004;256:145–152
  21. McAllister CG, van Kammen DP, Rehn TJ, Miller AL, Gurklis J, Kelley ME, et al. Increases in CSF levels of interleukin-2 in schizophrenia: effects of recurrence of psychosis and medication status. Am. J. Psychiatry. 1995;152:1291–1297
  22. Meisenzahl EM, Rujescu D, Kirner A, Giegling I, Kathmann N, Leinsinger G, et al. Association of an interleukin-1beta genetic polymorphism with altered brain structure in patients with schizophrenia. Am. J. Psychiatry. 2001;158:1316–1319
  23. Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of reporting of meta-analyses. Lancet. 1999;354:1896–1900
  24. Moots RJ, Al-Saffar Z, Hutchinson D, Golding SP, Young SP, Bacon PA, et al. Old drug, new tricks: haloperidol inhibits secretion of proinflammatory cytokines. Ann. Rheum. Dis. 1999;58:585–587
  25. Naudin J, Capo C, Giusano B, Mège JL, Azorin JM. A differential role for interleukin-6 and tumor necrosis factor-α in schizophrenia?. Schizophr. Res. 1997;26:227–233
  26. Nawa H, Takahashi M, Patterson PH. Cytokine and growth factor involvement in schizophrenia—support for the developmental model. Mol. Psychiatry. 2000;5:594–603
  27. Owen MJ, Craddock N, O'Donovan MC. Schizophrenia: genes at last. Trends Genet. 2005;21:518–525
  28. Owen MJ, Williams HJ, O'Donovan MC. Schizophrenia genetics: advancing on two fronts. Curr. Opin. Genet. Dev. 2009;19:266–270
  29. Papiol S, Rosa A, Gutiérrez B, Martín B, Salgado P, Catalán R, et al. Interleukin-1 cluster is associated with genetic risk for schizophrenia and bipolar disorder. J. Med. Genet. 2004;41:219–223
  30. Pociot F, Mølvig J, Wogensen L, Worsaae H, Nerup J. A TaqI polymorphism in the human interleukin-1β (IL-1β) gene correlates with IL-1β secretion in vitro. Eur. J. Clin. Invest. 1992;22:396–402
  31. Rapaport MH, McAllister CG, Pickar D, Tamarkin L, Kirch DG, Paul SM. CSF IL-1 and IL-2 in medicated schizophrenic patients and normal volunteers. Schizophr. Res. 1997;25:123–129
  32. Rosa A, Peralta V, Papiol S, Cuesta MJ, Serrano F, Martínez-Larrea A, et al. Interleukin-1beta (IL-1beta) gene and increased risk for the depressive symptom-dimension in schizophrenia spectrum disorders. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2004;124:10–14
  33. Rothwell NJ, Luheshi GN. Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci. 2000;23:618–625
  34. Saiz PA, Garcia-Portilla MP, Arango C, Morales B, Martinez-Barrondo S, Alvarez V, et al. Interleukin-1 gene complex in schizophrenia: an association study. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2006;141:678–680
  35. Shirts BH, Wood J, Yolken RH, Nimgaonkar VL. Association study of IL10, IL1beta, and IL1RN and schizophrenia using tag SNPs from a comprehensive database: suggestive association with rs16944 at IL1beta. Schizophr. Res. 2006;88:235–244
  36. Sirota P, Meiman M, Herschko R, Bessler H. Effects of neuroleptic administration on serum levels of soluble IL-2 receptor-alpha and IL-1 receptor antagonist in schizophrenic patients. Pschiatry Res. 2005;134:151–159
  37. Song C, Lin A, Kenis G, Bosmans E, Maes M. Immunosuppressive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist. Schizophr. Res. 2000;42:157–164
  38. St Clair D, Xu M, Wang P, Yu Y, Fang Y, Zhang F, et al. Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959–1961. JAMA. 2005;294:557–562
  39. Suzuki E, Shintani F, Kanba S, Asai M, Nakaki T. Induction of interleukin-1β and interleukin-1 receptor antagonist mRNA by chronic treatment with various psychotropics in widespread area of rat brain. Neurosci. Lett. 1996;215:201–204
  40. Swerdlow NR, Geyer MA. Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia. Schizophr. Bull. 1998;24:285–301
  41. Tatsumi M, Sasaki T, Sakai T, Kamijima K, Fukuda R, Kunugi H, et al. Genes for interleukin-2 receptor beta chain, interleukin-1 beta, and schizophrenia: no evidence for the association or linkage. Am. J. Med. Genet. 1997;74:338–341
  42. Tohmi M, Tsuda N, Watanabe Y, Kakita A, Nawa H. Perinatal inflammatory cytokine challenge results in distinct neurobehavioral alterations in rats: implication in psychiatric disorders of developmental origin. Neurosci. Res. 2004;50:67–75
  43. Toyooka K, Watanabe Y, Iritani S, Shimizu E, Iyo M, Nakamura R, et al. A decrease in interleukin-1 receptor antagonist expression in the prefrontal cortex of schizophrenic patients. Neurosci. Res. 2003;46:299–307
  44. Tsuda N, Tohmi M, Mizuno M, Nawa H. Strain-dependent behavioral alterations induced by peripheral interleukin-1 challenge in neonatal mice. Behav. Brain Res. 2006;166:19–31
  45. van Os J, Rutten BP, Poulton R. Gene–environment interactions in schizophrenia: review of epidemiological findings and future directions. Schizophr. Bull. 2008;34:1066–1082
  46. Watanabe Y, Nunokawa A, Kaneko N, Muratake T, Koizumi M, Someya T. Lack of association between the interleukin-1 gene complex and schizophrenia in a Japanese population. Psychiatry Clin. Neurosci. 2007;61:364–369
  47. Xu HM, Wei J, Hemmings GP. Changes of plasma concentrations of inerleukin-1α and interleukin-6 with neuroleptic treatment for schizophrenia. Br. J. Psychiatry. 1994;164:251–253
  48. Xu MQ, St Clair D, Ott J, Feng GY, He L. Brain-derived neurotrophic factor gene C-270T and Val66Met functional polymorphisms and risk of schizophrenia: a moderate-scale population-based study and meta-analysis. Schizophr. Res. 2007;91:6–13
  49. Xu MQ, Xing QH, Zheng YL, Li S, Gao JJ, He G, et al. Association of AKT1 gene polymorphisms with risk of schizophrenia and with response to antipsychotics in the Chinese population. J. Clin. Psychiatry. 2007;68:1358–1367
  50. Xu MQ, Sun WS, Liu BX, Feng GY, Yu L, Yang L, et al. Prenatal malnutrition and adult schizophrenia: further evidence from the 1959–1961 Chinese famine. Schizophr. Bull. 2009;35:568–576
  51. Yang J, Si T, Ling Y, Ruan Y, Han Y, Wang X, et al. Association study between interleukin-1beta gene (IL-1beta) and schizophrenia. Life Sci. 2003;72:3017–3021
  52. Zanardini R, Bocchio-Chiavetto L, Scassellati C, Bonvicini C, Tura GB, Rossi G, et al. Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia. J. Psychiatr. Res. 2003;37:457–462

PII: S0920-9964(10)01117-5

doi: 10.1016/j.schres.2010.02.1031

Schizophrenia Research
Volume 120, Issue 1 , Pages 131-142 , July 2010

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